TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5097	15514;15515;15516	chr2:178734535;178734534;178734533	chr2:179599262;179599261;179599260
N2AB	4780	14563;14564;14565	chr2:178734535;178734534;178734533	chr2:179599262;179599261;179599260
N2A	3853	11782;11783;11784	chr2:178734535;178734534;178734533	chr2:179599262;179599261;179599260
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-34
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.59
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/G	rs1230501060	-1.425	0.999	D	0.731	0.575	0.655633844924	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
E/G	rs1230501060	-1.425	0.999	D	0.731	0.575	0.655633844924	gnomAD-4.0.0	1.59678E-06	None	None	None	None	I	None	0	2.29347E-05	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.3122	likely_benign	0.2463	benign	-1.235	Destabilizing	0.998	D	0.656	neutral	D	0.545961201	None	None	I
E/C	0.9546	likely_pathogenic	0.9302	pathogenic	-0.62	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/D	0.498	ambiguous	0.3763	ambiguous	-1.179	Destabilizing	0.434	N	0.261	neutral	D	0.591157969	None	None	I
E/F	0.9014	likely_pathogenic	0.8623	pathogenic	-0.747	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/G	0.5654	likely_pathogenic	0.4514	ambiguous	-1.604	Destabilizing	0.999	D	0.731	prob.delet.	D	0.60620863	None	None	I
E/H	0.7118	likely_pathogenic	0.5981	pathogenic	-0.935	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
E/I	0.5468	ambiguous	0.4799	ambiguous	-0.211	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
E/K	0.2816	likely_benign	0.2204	benign	-0.74	Destabilizing	0.998	D	0.533	neutral	N	0.497687323	None	None	I
E/L	0.6075	likely_pathogenic	0.5193	ambiguous	-0.211	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/M	0.5985	likely_pathogenic	0.5486	ambiguous	0.359	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
E/N	0.6404	likely_pathogenic	0.5098	ambiguous	-1.191	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
E/P	0.9876	likely_pathogenic	0.9664	pathogenic	-0.533	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
E/Q	0.1919	likely_benign	0.1563	benign	-1.077	Destabilizing	0.999	D	0.643	neutral	N	0.510673167	None	None	I
E/R	0.4558	ambiguous	0.3612	ambiguous	-0.497	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/S	0.4334	ambiguous	0.3506	ambiguous	-1.612	Destabilizing	0.997	D	0.571	neutral	None	None	None	None	I
E/T	0.4503	ambiguous	0.362	ambiguous	-1.289	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
E/V	0.3582	ambiguous	0.2939	benign	-0.533	Destabilizing	1.0	D	0.765	deleterious	D	0.559519851	None	None	I
E/W	0.9741	likely_pathogenic	0.9625	pathogenic	-0.467	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/Y	0.8658	likely_pathogenic	0.8055	pathogenic	-0.462	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.